{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:24:31Z","timestamp":1768281871652,"version":"3.49.0"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"National Institute of Health","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"National Institute of Health","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"National Institute of Health","award":["CA217482"],"award-info":[{"award-number":["CA217482"]}]},{"name":"Georgia Cancer Coalition","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"Georgia Cancer Coalition","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"Georgia Cancer Coalition","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"Georgia Cancer Coalition","award":["CA217482"],"award-info":[{"award-number":["CA217482"]}]},{"name":"NIDDK R01 DK126080-01A1","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"NIDDK R01 DK126080-01A1","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"NIDDK R01 DK126080-01A1","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"NIDDK R01 DK126080-01A1","award":["CA217482"],"award-info":[{"award-number":["CA217482"]}]},{"name":"UT2AA028659-01","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"UT2AA028659-01","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"UT2AA028659-01","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"UT2AA028659-01","award":["CA217482"],"award-info":[{"award-number":["CA217482"]}]},{"name":"MBD fellowship, GSU","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"MBD fellowship, GSU","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"MBD fellowship, GSU","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"MBD fellowship, GSU","award":["CA217482"],"award-info":[{"award-number":["CA217482"]}]},{"name":"Center for Diagnosis and Therapeutics fellowship, GSU","award":["CA175112"],"award-info":[{"award-number":["CA175112"]}]},{"name":"Center for Diagnosis and Therapeutics fellowship, GSU","award":["CA118113"],"award-info":[{"award-number":["CA118113"]}]},{"name":"Center for Diagnosis and Therapeutics fellowship, GSU","award":["CA178730"],"award-info":[{"award-number":["CA178730"]}]},{"name":"Center for Diagnosis and Therapeutics fellowship, GSU","award":["CA217482"],"award-info":[{"award-number":["CA217482"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nonalcoholic steatohepatitis (NASH) and alcoholic hepatitis (AH) affect a large part of the general population worldwide. Dysregulation of lipid metabolism and alcohol toxicity drive disease progression by the activation of hepatic stellate cells and the capillarization of liver sinusoidal endothelial cells. Collagen deposition, along with sinusoidal remodeling, alters sinusoid structure, resulting in hepatic inflammation, portal hypertension, liver failure, and other complications. Efforts were made to develop treatments for NASH and AH. However, the success of such treatments is limited and unpredictable. We report a strategy for NASH and AH treatment involving the induction of integrin \u03b1v\u03b23-mediated cell apoptosis using a rationally designed protein (ProAgio). Integrin \u03b1v\u03b23 is highly expressed in activated hepatic stellate cells (\u03b1HSCs), the angiogenic endothelium, and capillarized liver sinusoidal endothelial cells (caLSECs). ProAgio induces the apoptosis of these disease-driving cells, therefore decreasing collagen fibril, reversing sinusoid remodeling, and reducing immune cell infiltration. The reversal of sinusoid remodeling reduces the expression of leukocyte adhesion molecules on LSECs, thus decreasing leukocyte infiltration\/activation in the diseased liver. Our studies present a novel and effective approach for NASH and AH treatment.<\/jats:p>","DOI":"10.3390\/ijms25137447","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:21:03Z","timestamp":1720441263000},"page":"7447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Depletion of Activated Hepatic Stellate Cells and Capillarized Liver Sinusoidal Endothelial Cells Using a Rationally Designed Protein for Nonalcoholic Steatohepatitis and Alcoholic Hepatitis Treatment"],"prefix":"10.3390","volume":"25","author":[{"given":"Falguni","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2310-7658","authenticated-orcid":false,"given":"Jenny J.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Payton","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiren","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1172\/JCI66369","article-title":"Hepatic stellate cells in liver development, regeneration, and cancer","volume":"123","author":"Yin","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.coi.2007.10.006","article-title":"Starring stellate cells in liver immunology","volume":"20","author":"Winau","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.5858\/2007-131-1728-HSCALF","article-title":"Hepatic stellate cells and liver fibrosis","volume":"131","author":"Moreira","year":"2007","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s10495-005-1055-4","article-title":"The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis","volume":"10","author":"Elsharkawy","year":"2005","journal-title":"Apoptosis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e170","DOI":"10.1038\/cddis.2011.52","article-title":"Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis","volume":"2","author":"Lim","year":"2011","journal-title":"Cell Death Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver","volume":"88","author":"Friedman","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1016\/j.biocel.2009.03.001","article-title":"Hepatic stellate cell: A star cell in the liver","volume":"41","author":"Atzori","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1002\/cphy.c120035","article-title":"Hepatic stellate cells and liver fibrosis","volume":"3","author":"Puche","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.4161\/cc.10.11.15828","article-title":"Hepatic stellate cells and astrocytes: Stars of scar formation and tissue repair","volume":"10","author":"Schachtrup","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.jhep.2008.12.011","article-title":"Angiogenesis in liver disease","volume":"50","author":"Semela","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.jhep.2010.07.004","article-title":"Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: New targets for the treatment of portal hypertension?","volume":"53","author":"Thabut","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1053\/j.gastro.2011.12.017","article-title":"Role of Differentiation of Liver Sinusoidal Endothelial Cells in Progression and Regression of Hepatic Fibrosis in Rats","volume":"142","author":"Xie","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1002\/hep.20193","article-title":"Angiogenesis in chronic inflammatory liver disease","volume":"39","author":"Medina","year":"2004","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1478-3231.2010.02369.x","article-title":"Angiogenesis in chronic liver disease and its complications","volume":"31","author":"Coulon","year":"2010","journal-title":"Liver Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.jhep.2014.05.047","article-title":"Vascular pathobiology in chronic liver disease and cirrhosis\u2014current status and future directions","volume":"61","author":"Iwakiri","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-5926-1-1","article-title":"Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: A review","volume":"1","author":"Braet","year":"2002","journal-title":"Comp. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1172\/JCI58789","article-title":"Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats","volume":"122","author":"Wang","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/hep.1840190308","article-title":"Endothelial activation and circulating vascular adhesion molecules in alcoholic liver disease","volume":"19","author":"Adams","year":"1994","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1530-0277.2009.01141.x","article-title":"Anti-Inflammatory and Anti-Apoptotic Roles of Endothelial Cell STAT3 in Alcoholic Liver Injury","volume":"34","author":"Miller","year":"2010","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2016.07.009","article-title":"Liver sinusoidal endothelial cells: Physiology and role in liver diseases","volume":"66","author":"Poisson","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"983","DOI":"10.4049\/jimmunol.169.2.983","article-title":"Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells","volume":"169","author":"Lalor","year":"2002","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1046\/j.1440-1711.2002.01062.x","article-title":"Recruitment of lymphocytes to the human liver","volume":"80","author":"Lalor","year":"2002","journal-title":"Immunol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4147","DOI":"10.4049\/jimmunol.1002961","article-title":"Common lymphatic endothelial and vascular endothelial receptor-1 mediates the transmigration of regulatory T cells across human hepatic sinusoidal endothelium","volume":"186","author":"Shetty","year":"2011","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/cmi.2016.5","article-title":"Immunological functions of liver sinusoidal endothelial cells","volume":"13","author":"Knolle","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41232-016-0005-6","article-title":"Roles of hepatic stellate cells in liver inflammation: A new perspective","volume":"36","author":"Fujita","year":"2016","journal-title":"Inflamm. Regen."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/hep.28112","article-title":"Hepatic stellate cells relay inflammation signaling from sinusoids to parenchyma in mouse models of immune-mediated hepatitis","volume":"63","author":"Fujita","year":"2016","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154542","DOI":"10.1016\/j.cyto.2018.09.004","article-title":"Role of hepatic stellate cell (HSC)-derived cytokines in hepatic inflammation and immunity","volume":"124","author":"Gupta","year":"2019","journal-title":"Cytokine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jcmgh.2018.01.003","article-title":"Neutrophil-Hepatic Stellate Cell Interactions Promote Fibrosis in Experimental Steatohepatitis","volume":"5","author":"Zhou","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jhep.2018.10.023","article-title":"Inflammatory pathways in alcoholic steatohepatitis","volume":"70","author":"Gao","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1002\/hep.27376","article-title":"Liver sinusoidal endothelial cells in hepatic fibrosis","volume":"61","author":"DeLeve","year":"2015","journal-title":"Hepatology"},{"key":"ref_32","first-page":"1011","article-title":"Hepatic myofibroblasts and fibrogenic progression of chronic liver diseases","volume":"30","author":"Novo","year":"2015","journal-title":"Histol. Histopathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/hep.22351","article-title":"Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence","volume":"48","author":"Deleve","year":"2008","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.bbadis.2012.11.002","article-title":"Extracellular matrix degradation in liver fibrosis: Biochemistry and regulation","volume":"1832","author":"Iredale","year":"2013","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/nm.3282","article-title":"Targeting of alphav integrin identifies a core molecular pathway that regulates fibrosis in several organs","volume":"19","author":"Henderson","year":"2013","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1172\/JCI93562","article-title":"The balancing act of the liver: Tissue regeneration versus fibrosis","volume":"128","author":"Huch","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1016\/j.ajpath.2018.03.008","article-title":"Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine","volume":"188","author":"Gilgenkrantz","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nature09493","article-title":"Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration","volume":"468","author":"Ding","year":"2010","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1172\/JCI66025","article-title":"Liver sinusoidal endothelial cells and liver regeneration","volume":"123","author":"DeLeve","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11675","DOI":"10.1038\/ncomms11675","article-title":"Rational design of a protein that binds integrin alphavbeta3 outside the ligand binding site","volume":"7","author":"Turaga","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Turaga, R.C., Satyanarayana, G., Sharma, M., Yang, J.J., Wang, S., Liu, C., Li, S., Yang, H., Grossniklaus, H., and Farris, A.B. (2021). Targeting integrin alphavbeta3 by a rationally designed protein for chronic liver disease treatment. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02611-2"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Carter, J.K., and Friedman, S.L. (2022). Hepatic Stellate Cell-Immune Interactions in NASH. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.867940"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.jhep.2019.02.012","article-title":"Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease","volume":"70","author":"Hammoutene","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3727\/105221617X695519","article-title":"Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance","volume":"17","author":"Gao","year":"2017","journal-title":"Gene Expr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1210\/er.2012-1009","article-title":"Diabetes and nonalcoholic Fatty liver disease: A pathogenic duo","volume":"34","author":"Williams","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.jhep.2011.08.025","article-title":"The interaction of hepatic lipid and glucose metabolism in liver diseases","volume":"56","author":"Bechmann","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jhep.2010.04.031","article-title":"Hepatocellular ballooning in NASH","volume":"53","author":"Caldwell","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15539","DOI":"10.3748\/wjg.v20.i42.15539","article-title":"Histopathology of nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis","volume":"20","author":"Takahashi","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jhep.2017.03.003","article-title":"CD44 is a key player in non-alcoholic steatohepatitis","volume":"67","author":"Patouraux","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1002\/hep4.1721","article-title":"Cluster of Differentiation 44 Promotes Liver Fibrosis and Serves as a Biomarker in Congestive Hepatopathy","volume":"5","author":"Osawa","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1053\/j.gastro.2011.09.002","article-title":"Alcoholic liver disease: Pathogenesis and new therapeutic targets","volume":"141","author":"Gao","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Guo, Q., Furuta, K., Islam, S., Caporarello, N., Kostallari, E., Dielis, K., Tschumperlin, D.J., Hirsova, P., and Ibrahim, S.H. (2022). Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.983255"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1172\/JCI73722","article-title":"Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis","volume":"125","author":"Weston","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/hep.23144","article-title":"Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis","volume":"50","author":"Patsenker","year":"2009","journal-title":"Hepatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"23996","DOI":"10.1074\/jbc.M311668200","article-title":"Engagement of alphavbeta3 integrin regulates proliferation and apoptosis of hepatic stellate cells","volume":"279","author":"Zhou","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/hep.24467","article-title":"Molecular imaging of hepatic stellate cell activity by visualization of hepatic integrin alphavbeta3 expression with SPECT in rat","volume":"54","author":"Li","year":"2011","journal-title":"Hepatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jhep.2012.07.046","article-title":"Liver sinusoidal endothelial cells in disease\u2014and for therapy?","volume":"58","author":"Stutchfield","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/hep.27332","article-title":"Hepatic inflammation and fibrosis: Functional links and key pathways","volume":"61","author":"Seki","year":"2015","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41575-018-0020-y","article-title":"Liver sinusoidal endothelial cells\u2014gatekeepers of hepatic immunity","volume":"15","author":"Shetty","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/wrr.12411","article-title":"PKM2 Released by Neutrophils at Wound Site Facilitates Early Wound Healing by Promoting Angiogenesis","volume":"24","author":"Zhang","year":"2016","journal-title":"Wound Repair Regen."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:11:14Z","timestamp":1760109074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,6]]},"references-count":60,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137447"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137447","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,6]]}}}